APA: Atypical Antipsychotic in Autism Safe Long Term

Action Points

Explain that aripiprazole (Abilify) appears to be well-tolerated and efficacious in treating irritability associated with autism, although patients were at risk for weight gain.

Add that in early trials, another atypical antipsychotic, paliperidone (Invega), appears to also be safe and effective for the condition.

Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

NEW ORLEANS -- The atypical antipsychotic aripiprazole (Abilify) appears to be safe for longer-term treatment of irritability associated with autism, but patients are at an increased risk of weight gain, researchers said here.

About a quarter of young patients had weight gains significantly above those expected with normal growth, Monique McCullough, PharmD, of drugmaker Bristol-Myers Squibb, said during a poster session at the American Psychiatric Association meeting here.

McCullough said weight increase was "our top concern" in the safety study, adding that there were "relatively few discontinuations due to adverse events."

Aripiprazole was approved in November 2009 to treat the irritability associated with autism. Only one other atypical antipsychotic -- risperidone (Risperdal) -- is approved for this indication.

Two posters presented here assessed year-long data on the safety and efficacy of aripiprazole for this indication following an eight-week, flexible-dose, randomized controlled trial. There were a total of 330 patients, including those who were in the earlier trial as well as de novo patients.

The majority of patients were males ages 6 to 12 and were taking doses ranging from 2 to 15 mg/day.

A total of 199 patients finished the 52-week trial; the most common reason for dropping out was because of an adverse event -- most frequently weight gain or aggression.

Generally, there were more adverse events in the de novo patients and those who were formerly on placebo, McCullough said, because those on the drug "had already been exposed."

The most common adverse event was weight increase, occurring in 23% of those previously taking aripiprazole, 22.9% among those formerly on placebo, and 23.3% of de novo patients.

The mean change in body weight z-score was 0.33 after nine months, but McCullough said weight gain appeared to plateau after six months.

McCullough and colleagues also assessed fasting metabolic abnormalities, some of which were significant. The most prevalent condition was a drop in HDL cholesterol, which was seen in 30% of patients.

They saw other significant metabolic abnormalities in glucose, total cholesterol, LDL cholesterol, and triglycerides, but none occurred in more than 7% of patients.

In the efficacy study, Meeta Patel, PharmD, also of Bristol-Myers Squibb, and colleagues found that the majority of patients were considered by clinicians to be "much" or "very much" improved (38.25% and 19.6%, respectively).

These improvements started early in treatment and were maintained over the course of the study, she said.

The researchers used the Aberrant Behavior Checklist-Irritability (ABC-I) scale, the Clinical Global Impression-Severity (CGI-S) and Improvement (CGI-I) scales to make their assessments.

For irritability and severity, they saw no significant changes from baseline for those who were already on aripiprazole, but improvements for former placebo and de novo patients.

Patel said that for those already on the drug, the improvement seen during the earlier part of the trial was sustained.

She added that all patients demonstrated improvements in health-related quality of life, and there was improvement in caregiver strain in both the prior placebo and de novo groups.

The studies were limited by their open-label nature, as the drug could not be measured against a control population.

Another atypical antipsychotic being evaluated as treatment for autism irritability is paliperidone (Invega), which is the major active metabolite of risperidone. Researchers say that because it's a metabolite, there's less potential for drug-drug interactions.

Stigler said during a poster session that 83% of patients were classified as responders based on improvements in CGI-I or ABC-I scores.

She said the mean baseline ABC-I was 30 and fell to 12.6 after eight weeks. The mean endpoint CGI-I was 1.6.

Overall, the drug appeared to be well-tolerated. but it too caused mild weight gain. About 80% of patients gained weight -- a mean of five pounds over the study period. Their mean body mass index (BMI) increased from 23.1 at baseline to 23.8 by the end of the study.

The researchers concluded that paliperidone may be effective for severe irritability in adolescents and adults with autism and appears to be well-tolerated, but larger trials are needed to investigate further.

Don Hilty, MD, of the University of California Davis, who wasn't involved in the research, said first-line treatments for the irritability associated with autism tend to be nonpharmacological, followed by antidepressants. Atypical antipsychotics are usually a third line of defense.

The aripiprazole study was funded by Bristol-Myers Squibb and Otsuka Pharmaceutical Co.

Patel and McCollough are employees of Bristol-Myers Squibb.

The paliperidone trial was funded by Janssen.

Stigler has received research support from Janssen and Bristol-Myers Squibb.

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